BGB-43395 / BeOne Medicines - LARVOL DELTA

BGB-43395 Plus Letrozole Versus CDK4/6i Plus Letrozole for Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Treatment for Advanced or Metastatic Disease (clinicaltrials.gov) - P3 | N=1056 | Not yet recruiting | Sponsor: BeOne Medicines

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Anticipated R&D Milestones (Businesswire) - "BGB-43395 (CDK4 inhibitor): Phase 3 trial initiation for the treatment of adult patients with first-line HR-positive, HER2-negative metastatic breast cancer: 1H 2026...BGB-B2033 (GPC3x41BB bispecific antibody): Potentially registrational Phase 2 trial initiation: 2H 2026."

New P2 trial • New P3 trial • Gastrointestinal Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

A Study of BG-75098 Alone and in Combination With Other Agents in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: BeOne Medicines | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Trial in progress: a phase 1 dose-escalation study evaluating BGB-21447 (BCL2 inhibitor) in combination with fulvestrant with and without BGB-43395 (CDK4 inhibitor) in patients with previously treated HR+/HER2− metastatic breast cancer (SABCS 2025) - P1 | "Patients with prior BCL2i exposure are excluded.Primary objectives are to assess the safety and tolerability of BGB-21447 in combination with fulvestrant, with or without BGB-43395, and to determine the maximum tolerated dose, maximum administered dose, and recommended dose for expansion of both the doublet and triplet combination. Secondary objectives are preliminary antitumor activity (objective response rate, duration of response, and time to response per Response Evaluation Criteria in Solid Tumors v1.1), characterization of the PK (single dose and steady state), and the preliminary effect of food on PK.This study is currently recruiting patients, with sites open across Australia, China, and the United States (Part A only)."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • BCL2L1 • CDKN2A • ER • HER-2

A Study of BG-75098 Alone and in Combination With Other Agents in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=105 | Not yet recruiting | Sponsor: BeOne Medicines

New P1 trial • Oncology • Solid Tumor

BG-68501-101: A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors (clinicaltrials.gov) - P1 | N=258 | Recruiting | Sponsor: BeiGene | Trial completion date: Feb 2028 ➔ Jul 2028

Platinum resistant • Trial completion date • Bladder Cancer • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: BeiGene | N=92 ➔ 120

Enrollment change • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BCL2

BGB-43395-103: A Study of Different Forms of BGB-43395 and Food Effect in Healthy Participants (clinicaltrials.gov) - P1 | N=51 | Completed | Sponsor: BeiGene | Active, not recruiting ➔ Completed | Trial completion date: Nov 2025 ➔ May 2025 | Trial primary completion date: Nov 2025 ➔ May 2025

Trial completion • Trial completion date • Trial primary completion date

BGB-43395-103: A Study of Different Forms of BGB-43395 and Food Effect in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ Nov 2025 | Trial primary completion date: May 2025 ➔ Nov 2025

Enrollment closed • Trial completion date • Trial primary completion date

BGB-43395 Alone or as Part of Combination Therapies in Participants With Breast Cancer and Other Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=300 | Recruiting | Sponsor: BeiGene | N=79 ➔ 300 | Trial completion date: May 2026 ➔ Jun 2028 | Trial primary completion date: May 2026 ➔ Jun 2028

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

BGB-43395-102: BGB-43395 Alone or as Part of Combination Therapies in Chinese Participants With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting | N=78 ➔ 33

Enrollment change • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

BG-68501-101: A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors (clinicaltrials.gov) - P1 | N=218 | Recruiting | Sponsor: BeiGene | N=138 ➔ 218

Enrollment change • Platinum resistant • Bladder Cancer • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

BeiGene Announces Fourth Quarter and Full Year 2024 Financial Results and Business Updates (Businesswire) - "Anticipate data readouts for BGB-43395 (CDK4 inhibitor), BG-68501 (CDK2 inhibitor) and BG-C9074 (B7H4 ADC) in the first half of 2025"

Clinical data • P1 data • Oncology • Solid Tumor

BeiGene Announces Fourth Quarter and Full Year 2024 Financial Results and Business Updates (Businesswire) - "Advan-TIG-302 (TIGIT antibody): anticipate interim data readout from Phase 3 study in first-line PD(L)1-high non small cell lung cancer in the second half of 2025...BGB-43395 (CDK4 inhibitor): continued dose escalation in monotherapy and in combination with fulvestrant and letrozole in the anticipated efficacious dose range; more than 180 patients enrolled to date and proof-of-concept expected in the first half of 2025...Zanidatamab (HER2 bispecific antibody) in combination with tislelizumab and chemotherapy: anticipate primary PFS data readout from Phase 3 study in first-line HER2-positive gastroesophageal adenocarcinoma in the second half of 2025...BGB-45035 (IRAK4 CDAC): currently in dose escalation in both SAD and MAD cohorts with more than 130 subjects enrolled...Phase 2 study planned in 2025; proof-of-concept for tissue IRAK4 degradation in the second half of 2025."

Clinical data • New P2 trial • Breast Cancer • Gastroesophageal Cancer • Immunology • Non Small Cell Lung Cancer

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BCL2

BGB-43395-103: A Study of Different Forms of BGB-43395 and Food Effect in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=92 | Not yet recruiting | Sponsor: BeiGene

New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BCL2

A Study of Different Forms of BGB-43395 and Food Effect in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: BeiGene

New P1 trial

Company News丨BeiGene Announces Breast Cancer Pipeline [Google translation] (bydrug.pharmcube.com) - "Recently, BeiGene...presented for the first time at the San Antonio Breast Cancer Symposium (SABCS) and announced the latest data on the company's breast cancer treatment product portfolio. Poster presentations included first-in-human data from BeiGene's investigational cyclin-dependent kinase (CDK) 4 inhibitor BGB-43395 for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer patients. Two posters highlighted the ongoing trial designs for BGB-43395 and CDK2 inhibitor BG-68501/EXT-197, and one poster detailed the preclinical characteristics of BGB-43395."

P1 data • Preclinical • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Preclinical characterization of BGB-43395, a potential best-in-class CDK4 selective inhibitor with potent pharmacodynamic and anti-tumor activity in HR+HER2- breast cancer models (SABCS 2024) - P1 | "In the biochemical assay, BGB-43395 exhibits superior kinase inhibition against CDK4 compared to approved CDK4/(6) inhibitors (palbociclib, ribociclib and abemaciclib) and investigational CDK4 inhibitor PF-07220060...BGB-43395 in combination with fulvestrant also demonstrated a greater tumor growth inhibition compared to palbociclib in combination with fulvestrant in HR+HER2- MCF7 xenograft models. In summary, BGB-43395 is a potential best-in-class CDK4 inhibitor with high potency and selectivity over CDK6 and other kinases, providing an opportunity to achieve high exposure and thus maximum on-target CDK4 inhibition for the treatment of HR+HER2- breast cancer and other CDK4 dependent cancers. BGB-43395 is currently undergoing clinical investigation as monotherapy or in combination with endocrine therapies in patients with metastatic HR+HER2- BC and other advanced solid tumors (NCT06120283)."

PK/PD data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • RB1

First-in-human phase 1a, dose-escalation study of BGB-43395 (CDK4-selective inhibitor) as monotherapy and in combination with fulvestrant or letrozole in patients with metastatic HR+/HER2+ breast cancer and other advanced solid tumors (SABCS 2024) - P1 | "BGB-43395 is a novel CDK4-selective inhibitor and a promising agent for tumors with high CDK4 dependency with the potential to minimize off-target toxicity. To date, BGB-43395 has been safe and tolerable, supporting continued development. The dose-escalation phase is currently ongoing."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDKN2A • HER-2

Trial in progress: First-in-human phase 1a/1b, dose-escalation/expansion study of BGB-43395 (CDK4 selective inhibitor) as monotherapy or combination therapy in Chinese patients with metastatic HR+/HER2- breast cancer & other advanced solid tumors (SABCS 2024) - P1 | " This phase 1a/1b, open-label, multicenter study is evaluating the safety, tolerability, PK, pharmacodynamics (PD), and preliminary antitumor activity of BGB-43395 given orally as monotherapy or in combination with fulvestrant, letrozole, or other combination partners in Chinese pts with advanced or metastatic solid tumors, including HR+/HER2− BC (NCT06253195). Exploratory endpoints are overall survival and potential biomarkers associated with response. As of May 28, 2024, the study is currently enrolling pts, with five pts currently dosed in the dose-escalation phase across 12 sites in China."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

BG-68501-101: A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors (clinicaltrials.gov) - P1 | N=138 | Recruiting | Sponsor: BeiGene | Trial completion date: Dec 2026 ➔ Feb 2028 | Trial primary completion date: Dec 2026 ➔ Feb 2028

Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

BeiGene (06160)'s Class 1 new drug BGB-43395 tablets approved for clinical use in breast cancer and other solid tumors [Google translation] (Sina Corp) - "On August 22, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that BeiGene's...Class 1 new drug BGB-43395 tablets were approved for clinical use, and are intended to be used as a single-drug treatment or in combination with fulvestrant, letrozole or other drugs to treat advanced or metastatic HR+/HER2- breast cancer and other solid tumors...More than 60 patients have been enrolled so far, and the first data readout results of the Phase 1 trial are expected to be announced in the fourth quarter of 2024."

P1 data • Trial status • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

BeiGene Reports First Quarter 2024 Financial Results and Business Updates (Businesswire) - "BGB-43395 (CDK4 inhibitor): Initiated fourth dose level of monotherapy, which is in the efficacious dose range with no dose limiting toxicities observed; and initiated dosing of combination with fulvestrant just over four months from first monotherapy dose. BG-68501 (CDK2 inhibitor): Initiated second dose level of monotherapy in first-in-human study, with clinical pharmacokinetics as expected and no dose limiting toxicities observed. BG-C9074 (B7H4 ADC): First patient dosed in Australia in global first-in-human Phase 1 study."

Trial status • Endometrial Cancer • Gastric Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor